Abnormal lipid metabolism and disease caused by deficiency of atypical secretory phospholipase A2 (sPLA2-III)

• Project/Area Number: 21890310
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: SATO Hiroyasu Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 研究員 (50546629)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000); Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000); Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
• Keywords: 脂質 / ホスホリパーゼA2 / 生殖 / メタボリックシンドローム / メタボリックシンドロ

Research Abstract

We have shown that group III phospholipase A2 (sPLA2-III), a member of the secreted phospholipase A2 (sPLA2) family, is expressed in the mouse proximal epididymal epithelium and that targeted disruption of the gene encoding this protein (Pla2g3) leads to defects in sperm maturation and fertility. Our results reveal a role for the atypical sPLA2 family member sPLA2-III in epididymal lipid homeostasis and indicate that its perturbation may lead to sperm dysfunction. Additionally, sPLA2-III was expressed constitutively in preadipocytic cells in the stromal vascular fraction of white adipose tissue. High-fat diet induced obesity, steatohepatitis, hyperlipidemia, hyperglycemia and insulin resistance were ameliorated in Pla2g3-/- mice. Adipose or hepatic expression of lipogenic, adipogenic and proinflammatory genes and adipose level of lysophosphatidylcholine were significantly reduced in Pla2g3-/- mice compared with wild-type mice.

Research Products

• [Journal Article] Hair follicular expression and function of group X secreted phospholipase A_2 in mouse skin. (2011)
  • Author(s): Yamamoto K, Taketomi T, Isogai Y, Miki Y, Sato H, Masuda S, Nishito Y, Morioka K, Ishimoto Y, Suzuki N, Yokoya Y, Hanasaki K, Ishikawa Y, Ishii T, Kobayashi T, Fukami K, Ikeda K, Nakanishi H, Taguchi R, Murakami M
  • Journal Title: J Biol Chem. 286 Pages: 11616-11631
  • Peer Reviewed
• [Journal Article] Physiological roles of group X secreted phospholipase A_2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function. (2011)
  • Author(s): Sato H, Isogai Y, Masuda S, Taketomi Y, Miki Y, Kamei D, Hara S, Kobayashi T, Ishikawa Y, Ishii T, Ikeda K, Taguchi R, Ishimoto Y, Suzuki N, Yokota Y, Hanasaki K, Suzuki-Yamamoto T, Yamamoto K, Murakami M
  • Journal Title: J Biol Chem. 286 Pages: 11632-11648
  • Peer Reviewed
• [Journal Article] Recent progress in phospholipase A_2 research : from cells to animals to humans. (2011)
  • Author(s): Murakami M, Taketomi Y, Miki Y, Sato H, Hirabayashi T, Yamamoto K
  • Journal Title: Prog Lipid Res. 50 Pages: 152-192
  • Peer Reviewed
• [Journal Article] Physiological roles of group X secreted phospholipase A_2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function (2011)
  • Author(s): Sato, et al
  • Journal Title: The Journal of Biological Chemistry Volume: 286 Pages: 11632-11648
  • Peer Reviewed
• [Journal Article] Group III secreted phospholipase A_2 regulates epididymal sperm maturation and fertility in mice. (2010)
  • Author(s): Sato H, Taketomi T, Isogai Y, Miki Y, Yamamoto K, Masuda S, Hosono T, Arata S, Ishikawa Y, Ishii T, Kobayashi T, Nakanishi H, Ikeda K, Taguchi R, Hara S, Kudo I, Murakami M
  • Journal Title: J Clin Invest. 120 Pages: 1400-1414
  • Peer Reviewed
• [Journal Article] Group X phospholipase A_2 is released during sperm acrosome reaction and controls fertility outcome in mice. (2010)
  • Author(s): Escoffier J, Jemel I, Tanemoto A, Taketomi Y, Payre C, Coatrieux C, Sato H, Yamamoto K, Masuda S, Pernet-Gallay K, Pierre V, Hara S, Murakami M, De Waard M, Lambeau G, Arnoult C
  • Journal Title: J Clin Invest. 120 Pages: 1415-1428
  • Peer Reviewed
• [Journal Article] Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice (2010)
  • Author(s): Hiroyasu Sato
  • Journal Title: The Journal of clinical investigation (In press)
  • Peer Reviewed
• [Journal Article] Group III secreted phospholipase A_2 transgenic mice spontaneously develop inflammation. (2009)
  • Author(s): Sato H, Taketomi Y, Isogai Y, Masuda S, Kobayashi T, Yamamoto K, Murakami M
  • Journal Title: Biochem J. 421 Pages: 17-27
  • Peer Reviewed
• [Journal Article] Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation (2009)
  • Author(s): Hiroyasu Sato
  • Journal Title: The Biochemical journal 421 Pages: 17-27
  • Peer Reviewed
• [Presentation] 「生命薬学における精子バイオロジーと脂質ネットワーク」ホスホリパーゼA_2による精子成熟と活性化の制御 (2011)
  • Author(s): 佐藤弘泰、村上誠
  • Organizer: 日本薬学会第131年会シンポジウム
  • Place of Presentation: 静岡市
  • Year and Date: 2011-03-29
• [Presentation] 「生命薬学における精子バイオロジーと脂質ネットワーク」ホスホリパーゼA_2による精子成熟と活性化の制御 (2011)
  • Author(s): 佐藤弘泰
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡(招待講演)
  • Year and Date: 2011-03-29
• [Presentation] フタル酸モノエステル類のホスホリパーゼA_2活性阻害を介したマウス精子受精能の抑制 (2011)
  • Author(s): 原俊太郎、種本明生、加藤洋幸、佐藤弘泰、武富芳隆、村上誠
  • Organizer: 第81回日本衛生学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-28
• [Presentation] Suppression of sperm fertility by monophthalate via inhibiting spermatozoal phospholipase A_2 activity. (2011)
  • Author(s): Hara S, Taketomi Y, Sato H, Murakami M
  • Organizer: SOT Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] sPLA_2-V, an adipocyte-inducible metabolic sPLA_2, controls systemic lipid metabolism. (2010)
  • Author(s): 佐藤弘泰、武富芳隆、山本圭、石川由紀雄、石井寿晴、原俊太郎、村上誠
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] sPLA_2-III, a mast cell-derived anaphylactic sPLA_2, regulates mast cell-dependent anaphylactic response. (2010)
  • Author(s): 武富芳隆、佐藤弘泰、田中智之、中村正則、上野紀子、西藤泰昌、山本圭、杉本幸彦、原俊太郎、村上誠
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] sPLA_2-V, an adipocyte-inducible metabolic sPLA_2, controls systemic lipid metabolism. (2010)
  • Author(s): 佐藤弘泰
  • Organizer: Biochemistry and Molecular Biology BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] III型分泌性ホスホリパーゼA_2の欠損はメタボリックシンドロームを改善する (2010)
  • Author(s): 佐藤弘泰、磯貝有紀、武富芳隆、山本圭、石川由紀雄、石井壽晴、小林哲幸、中西広樹、池田和貴、田口良、原俊太郎、村上誠
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 群馬
  • Year and Date: 2010-06-15
• [Presentation] III型分泌性ホスホリパーゼA_2の欠損はメタボリックシンドロームを改善する (2010)
  • Author(s): 佐藤弘泰
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 群馬県伊香保
  • Year and Date: 2010-06-15
• [Presentation] Group III secreted phospholipase A_2 regulates epididymal sperm maturation and fertility in mice (2010)
  • Author(s): Hiroyasu Sato
  • Organizer: Keystone Symposia
  • Place of Presentation: ウェスティン都ホテル京都
  • Year and Date: 2010-06-09
• [Presentation] New insights into the functions of secreted phospholipase A_2s : sPLA_2 in reproduction. (2010)
  • Author(s): Sato H, Taketomi Y, Yamamoto K, Arnoult C, Lambeau G, Murakami M
  • Organizer: 7th GERLI Lipidmics Congress
  • Place of Presentation: France
• [Presentation] Group III secreted phospholipase A_2 regulates epididymal sperm maturation and fertility in mice. (2010)
  • Author(s): Sato H, Taketomi Y, Yamamoto K, Murakami M
  • Organizer: Keystone Symposia.
  • Place of Presentation: Kyoto, Japan
• [Presentation] Recent insights into the multiple molecular and functional properties of group X sPLA_2. (2010)
  • Author(s): Lambeau G, Jemel J, Escoffier J, Ait-Oufella H, Hiromi Li H, Guillaume C, Gora S, Surrel F, Coatrieux C, Payre C, Taketomi Y, Sato H, Yamamoto K, Arnoult C, Mallat Z, Gelb M.H, Deregnaucourt C, Ninio E, Karabina S, Murakami M.
  • Organizer: Keystone Symposia
  • Place of Presentation: Kyoto, Japan
• [Presentation] III型分泌性ホスホリパーゼA_2 は精子成熟を制御する (2009)
  • Author(s): 佐藤弘泰、武富芳隆、山本圭、磯貝有紀、三木寿美、小林哲幸、池田和貴、中西広樹、田口良、原俊太郎、村上誠
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] III型分泌性ホスホリパーゼA_2はマスト細胞の分化成熟を制御する (2009)
  • Author(s): 武富芳隆、佐藤弘泰、田中智之、上野紀子、山本圭、原俊太郎、村上誠
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] III型分泌性ホスホリパーゼA_2は精子成熟を制御する (2009)
  • Author(s): 佐藤弘泰
  • Organizer: 第82回生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-21
• [Presentation] III型分泌性ホスホリパーゼA_2は精子成熟を制御する (2009)
  • Author(s): 佐藤弘泰、武富芳隆、磯貝有紀、三木寿美、山本圭、石川由紀雄、石井壽晴、小林哲幸、中西広樹、池田和貴、田口良、原俊太郎、村上誠
  • Organizer: 第29回日本脂質生化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-31
• [Presentation] III型分泌性ホスホリパーゼA_2はマスト細胞依存性の即時性アレルギーに関わる (2009)
  • Author(s): 武富芳隆、佐藤弘泰、田中智之、上野紀子、山本圭、田口良、工藤一郎、原俊太郎、村上誠
  • Organizer: 第29回日本脂質生化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-31
• [Presentation] III型分泌性ホスホリパーゼA_2は精子成熟を制御する (2009)
  • Author(s): 佐藤弘泰
  • Organizer: 第51回 日本脂質生化学会
  • Place of Presentation: 名古屋 ウィルあいち
  • Year and Date: 2009-07-31
• [Presentation] Impaired sperm maturation and fertility in group III phospholipase A_2-defficient mice (2009)
  • Author(s): 佐藤弘泰
  • Organizer: 4^<th> International Conference on Phosphplipase A_2 and Lipid Mediatoers
  • Place of Presentation: 東京 学術総合センター
  • Year and Date: 2009-05-27
• [Presentation] Impaired sperm maturation and fertility in group III phospholipase A_2-deficient mice. (2009)
  • Author(s): Sato H, Taketomi Y, Isogai Y, Yamamoto K, Murakami M
  • Organizer: The 4th International Conference on Phospholipase A_2s and Lipid Mediators
  • Place of Presentation: Tokyo, Japan
• [Presentation] Group III phospholipase A_2 in stromal fraction of adipose tissue controls systemic lipid metabolism. (2009)
  • Author(s): Isogai Y, Sato H, Taketomi Y, Yamamoto K, Kobayashi T, Murakami M
  • Organizer: The 4th International Conference on Phospholipase A_2s and Lipid Mediators
  • Place of Presentation: Tokyo, Japan
• [Presentation] Group III secreted phospholipase A_2, an endogenous bee venom phospholipase A_2 homolog, is a crucial regulator of mast cell maturation and functions. (2009)
  • Author(s): Taketomi Y, Sato H, Ueno N, Yamamoto K, Murakami M
  • Organizer: The 4th International Conference on Phospholipase A_2s and Lipid Mediators
  • Place of Presentation: Tokyo, Japan
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